Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.94 mg/m³
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.67 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
43
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Critical NOAEL used = rat oral NOAEL 30 mg/kg/day (28-day repeated dose)

Critical NOAEL used = rabbit dermal NOAEL 30 mg/kg/day (repeated dose dermal – systemic)

Absorption rates: 10% dermal, 100% oral, and 100% inhalation regardless of species

 

Dermal - Systemic

Dose descriptor = NOAEL of 30 mg/kg/day

 

Modification of dose descriptor

= dermal NOAEL * (animal exposure / worker exposure) * (animal days / worker days)

= 30 * (24 / 8) * (4 / 5)

dermal NOAEL = 72 mg/kg/day

Adjustment factors (ECETOC):

allometric scaling          2.4

workers                       3

subacute study             6

           

DNEL calculation

DNEL dermal = dermal NOAEL / (adjustment factors)

DNEL dermal = 72 mg/kg/day / (2.4 * 3 * 6)

DNEL dermal = 1.67 mg/kg/day

  

Inhalation

Dose descriptor = NOAEL of 30/mg/kg/day

 

Route-to-route extrapolation (calculation B.3 in ECHA Guidance R.8)

inhalatory NOAEC = oral NOAEL * (1/ sRV rat 8h) * (ABS oral / ABS inh) * (sRV human / wRV)

inhalatory NOAEC= 30 * (1/0.38) * (100/100) * (6.7 / 10)

inhalatory NOAEC = 52.89 mg/m3

Adjustment factors (ECETOC):

allometric scaling:         not applied based on calculation method

workers                       3

subacute study             6

           

DNEL calculation

DNEL inhalation = inhalation NOAEC / (adjustment factors)

DNEL inhalation = 52.89 mg/m3 / (3 * 6)

DNEL inhalation = 2.94 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 mg/m³
DNEL related information
Overall assessment factor (AF):
30
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.24 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Critical NOAEL used = rat oral NOAEL 30 mg/kg/day (28-day repeated dose)

Critical NOAEL used = rabbit dermal NOAEL 30 mg/kg/day (repeated dose dermal – systemic)

Absorption rates: 10% dermal, 100% oral, and 100% inhalation regardless of species

 

Dermal - Systemic

Dose descriptor = NOAEL of 30 mg/kg/day

 

Modification of dose descriptor

= dermal NOAEL * (animal exposure / worker exposure) * (animal days / worker days)

= 30 * (24 / 24) * (4 / 7)

dermal NOAEL = 17.14 mg/kg/day

Adjustment factors (ECETOC):

allometric scaling          2.4

population                   5

subacute study             6

           

DNEL calculation

DNEL dermal = dermal NOAEL / (adjustment factors)

DNEL dermal = 17.14 mg/kg/day / (2.4 * 5 * 6)

DNEL dermal = 0.24 mg/kg/day

  

Inhalation

Dose descriptor = NOAEL of 30 mg/kg/day

 

Route-to-route extrapolation (calculation B.3 in ECHA Guidance R.8)

inhalatory NOAEC = oral NOAEL * (1/ sRV rat 24h) * (ABS oral / ABS inh)

inhalatory NOAEC= 30 * (1/1.15) * (100/100)

inhalatory NOAEC = 26.09 mg/m3

Adjustment factors (ECETOC):

allometric scaling:         not applied based on calculation method

population                   5

subacute study             6         

 

DNEL calculation

DNEL inhalation = inhalation NOAEC / (adjustment factors)

DNEL inhalation = 26.09 mg/m3 / (5 * 6)

DNEL inhalation = 0.87 mg/m3

Oral

Dose descriptor = NOAEL of 30 mg/kg/day

 

Modification of dose descriptor: Not required

 

Adjustment factors (ECETOC):

allometric scaling          4

population                   5

subacute study             6

 

DNEL calculation

DNEL oral = oral NOAEL / (adjustment factors)

DNEL oral = 30 mg/kg/day / (120)

DNEL dermal = 0.25 mg/kg/day